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Cross-Dehydrogenative Coupling Facilitated by Iron Mediated C–H Functionalization Adjacent to π Bonds
No full textThe functionalization of C–H bonds adjacent to π bonds offers great opportunity for the diversification of synthetically useful molecules. The integration of this C–H functionalization strategy with cross-dehydrogenative coupling (CDC), which eliminates the necessity for substrate prefunctionalization, is a useful alternative for the synthesis of functionalized molecules from readily available starting materials. Herein, this dissertation describes two distinct strategies for iron-mediated cross-dehydrogenative coupling using alkyne and allene precursors.
The regioselective coupling of unactivated allenes and tetrahydroisoquinolines (THIQs) was achieved via the in-situ formation of a nucleophilic organometallic species through iron-assisted allenic C–H deprotonation, followed by its addition to dihydroisoquinolinium electrophile, which was obtained from tetrahydroisoquinoline via hydride abstraction. The transformation represented a compelling approach for the quick assembly and diversification of C1 substituted tetrahydroisoquinolines, which are prevalent scaffolds in natural products and bioactive compounds.
A distinct strategy for the chemo- and regioselective coupling of alkynes and alcohols was next developed. A nucleophilic organoiron species was prepared from alkyne via iron-assisted propargylic C–H deprotonation. In contrast to prior strategies based on electrophilic functionalization, this cross-dehydrogenative coupling reaction leveraged oxidation induced reversal of reactivity of this organometallic complex, facilitating subsequent coupling with alcohol nucleophiles. This unique organometallic umpolung approach enabled the previously unattained etherification of propargylic C–H bonds and proceeded with excellent functional group tolerance and chemoselectivity. Our findings revealed that the oxidant’s oxidation potential and electron transfer efficiency between oxidant and organoiron species correlated well with reactivity. Mechanistic studies suggested that a transient intermediate with radical character was generated via single-electron oxidation of the organoiron species
Biological Applications and Mechanistic Insights of Ligand-Accelerated Palladium-Catalyzed O-Deallylation
No full textThis thesis discusses the biological activity and mechanistic aspects of the ligand-accelerated palladium-catalyzed O-deallylation. Previously, Pohorilets (Koide Group) reported a tri(2-furyl)phosphine (TFP) analog, iPhos, which successfully uncaged resorufin allyl ether in cell culture media containing serum. The primary objective of the current work is to evaluate the kinetics of Pd(OAc)2-iPhos, investigate its activity in living cells, and explore its potential in bioorthogonal applications. Pd(OAc)2-iPhos outperformed a benchmark Ru complex in complete culture media, yielding a second-order rate constant of 36.2 M-1s-1. The high bioorthogonal activity was also demonstrated in intracellular uncaging of allyl Pittsburgh Green ether. The uncaging can not only be performed in living cells maintained in HBSS, but also in living cells maintained in complete culture media. Complete culture media contains proteins and vitamins abundantly to sustain the cell growth, and such biological matrix is detrimental for transition metals. Therefore, the compatibility of Pd(OAc)2-iPhos with complete culture media highlights the improvement of Pd catalyst for using under a bioorthogonal context.
The high activity of Pd(OAc)2-iPhos was corroborated by cryogenic 31P NMR. The addition of Pd(OAc)2 to the solution of iPhos broadened the peak corresponding to iPhos, indicating the rapid equilibrium between the Pd-bound and unbound iPhos. This broadened peak became sharper as the temperature decreased. Importantly, this observation was absent with Pd(OAc)2-TFP. The cryogenic 31P NMR studies suggested that a labile Pd-P interaction facilitates the catalytic activity likely by enhancing the π-philicity of the Pd center.
To explore other applications for Pd(OAc)2-iPhos, uncaging of caged nuclear localization signal (NLS), delivering membrane-impermeable aspartate and small molecules were tested. Pd(OAc)2-iPhos was unable to achieve the desired outcome. However, these failed attempts offered new insights into the future applications of Pd(OAc)2-iPhos.
Collectively, current work reported Pd(OAc)2-iPhos, a highly bioorthogonally active Pd-phosphine complex which remained active in living cells within an unmodified cell culture environment. The mechanistic insights provided by cryogenic 31P NMR suggest that the π-philic nature of Pd complex was crucial for the bioorthogonal activity. The present study on Pd complex added valuable insights for the future development of bioorthogonal Pd catalysts
Peer Support: A Nontraditional Treatment Addition for People with Eating Disorders
No full textEating disorders are an important public health issue because there is limited accessibility to diagnosis and treatment and a lack of understanding and awareness from the public, healthcare professionals, and policymakers. Eating disorders are serious and complex mental illnesses with a variety of different diagnoses. In the peer support intervention model, an individual well into recovery guides another individual who is beginning the recovery process by offering emotional support, access to recovery resources, practical recovery tips and advice, and most importantly, a listening ear. Peer support has the potential to mitigate disparities in eating disorder treatment, encourage and reinforce recovery, and prevent relapse when used as an addition to typical treatment methods. Very little is known about peer support for people with eating disorders, but there is significant research on the benefits of its use with other mental health conditions, making it a promising addition to standard treatment methods for people with eating disorders. This paper argues the position that peer support is a valid treatment addition for people with eating disorders and that peer supporters should be integrated into eating disorder treatment teams. Information regarding the current landscape of eating disorders, the treatment standards and eating disorder recovery will be discussed. Peer support and its history, mechanisms and uses will also be discussed. Lastly, the application of the information discussed will be used to argue the addition and integration of peer support to treatment teams for people with eating disorders
Social, Structural and Sexuality Influences on Acute Alcohol-Related Harms: Unifying Conceptual Models for Young Adults
No full textAcute alcohol-related harms disproportionately impact sexual minority young adults compared to cisgender, heterosexual young adults. This stands true even when accounting for the amount of alcohol consumed, which suggests that other factors contribute to this relationship. The purpose of this study was to understand the factors that impact this inequitable relationship between acute alcohol-related harms and sexual minority young adults. The goal of this study was to co-create a community-informed, theory-based conceptual model with LGBTQ+ community members to illustrate the social and structural factors that contribute to the increased prevalence of acute alcohol-related harms for this specific population. There were six community collaborative sessions held where community members participated in human-centered design activities that helped foster idea generation in order to design a conceptual model. The final version of the conceptual model includes factors like poor mental health, discrimination, social constraints in the drinking context, lack of community support, and financial burden. The results from this study hope to inform future interventions to decrease incidents of acute alcohol-related harms for sexual minority young adults
The Association Between Self-Compassion and Sleep Among Midlife Women
No full textFor many women, midlife and the menopause transition is a period of increased risk for a variety of physical and mental health changes and symptoms, including sleep and mood disturbances. Sleep quality plays a critical role in mental and physical health outcomes. Positive psychological states, such as self-compassion, may be associated with improved sleep quality. Self-compassion may also be associated with better mental health, which in turn may have implications for sleep. We tested whether greater self-compassion was associated with improved sleep quality and fewer insomnia symptoms among 274 midlife women aged 45-67. The role of depressive symptoms and anxiety were also considered in these associations. Greater self-compassion was associated with better sleep quality [B(SE)=-0.027(.006), p<0.001, multivariable] and lower insomnia symptoms [B(SE)=-0.209(.084), p=.013, multivariable] after adjusting for confounders. Mood symptoms, including depression and anxiety, emerged as significant partial and full mediators, respectively, of the relationship between self-compassion and sleep. These findings have important public health implications, as interventions to improve women’s self-compassion may reduce the negative physiologic and psychological health effects of the menopause transition by improving mood, which in turn can improve sleep
Evaluating Epidemiological Trends and Public Health Risks in Climate Change-Related Disasters: Leveraging a One Health Approach for Integrated Solutions
No full textThis essay examined the intersection of climate change, natural disasters, and public health
outcomes, with a particular focus on the increased risks of vector-borne diseases. Using the One
Health Systems Mapping and Analysis Resource Toolkit (OH-SMART) framework, the analysis
evaluated two case studies of climate-related disasters: the 2022 floods in Pakistan and the 2017
impacts of Hurricanes Maria and Irma in Puerto Rico. The OH-SMART framework, previously
operationalized in 18 countries, was chosen for its adaptability and effectiveness in disaster
preparedness and vector-borne disease control, particularly in low-resource settings. Each of the
framework’s six steps was applied to the case studies to analyze existing disaster responses and
identify gaps where interdisciplinary strategies could have improved outcomes.
Case Study 1 focused on the hydrological disaster of the 2022 Pakistan floods, which
exacerbated the transmission of vector-borne diseases. The case study analysis highlighted the
importance of incorporating local stakeholders into environmental surveillance to address disease
outbreaks effectively. Case Study 2 examined the meteorological disasters of Hurricanes Maria
and Irma in Puerto Rico, which caused widespread disruption to public health systems,
infrastructure, and mosquito surveillance, increasing the risks of arboviral diseases such as dengue
and Zika. By employing the six steps of the OH-SMART framework, this essay demonstrated the
critical need for cross-sectoral collaboration. Ultimately, the findings argued that climate-related
disasters required proactive, multidisciplinary One Health approaches to mitigate cascading public
health impacts and build sustainable, community-centered solutions for disaster preparedness,
response, and recovery
Animal Bite Surveillance in Allegheny County, Pennsylvania, 2023
No full textBackground: Animal bites are a common injury and significant public health issue due to potential transmission of rabies, a viral pathogen fatal to humans when untreated. Healthcare providers are legally required to report animal bites involving humans to the Allegheny County Health Department (ACHD), which are investigated by ACHD staff. Previous literature utilized emergency department (ED) data to estimate bite incidence and suggested bite underreporting is common. The objectives of this analysis are to analyze reported bites to ACHD, compare characteristics of reported bites to ED data, and evaluate bite reporting completeness.
Methods: Bite reports for Allegheny County residents in 2023 were entered by healthcare providers or ACHD staff to an Oracle database. Separate data from emergency department (ED) visits in Allegheny County in 2023 with ICD-10 discharge codes pertaining to bites were obtained through EpiCenter surveillance system. Both datasets were imported to SAS and Microsoft Excel for analysis. ArcGIS Pro was used to verify reported bites occurred within the county or had county resident involvement. Population estimates were obtained from U.S. Census Bureau.
Results: ACHD received 2,157 unique mammal bite reports in 2023. Bites were primarily from dogs (76.2%) or cats (20.4%). Victims were more likely to be female (57.9%) and young adults; 25- to 29-year-olds had the highest bite rate by age group. Of reports with treatment location (49.3%), most victims were treated in urgent care centers (29.4%) or hospitals (17.5%). ED data contained 1,370 bite-related visits. By animal species, victim sex, and victim age, bites treated in EDs were similar to ACHD reported bites, although ED visits for raccoon bites (12) outnumbered raccoon bites reported to ACHD (4).
Conclusion: Dogs or cats were responsible for most bites. ED visit data was mostly consistent with county reported bites but suggested underreporting of bites from raccoons, which are a species with elevated risk for rabies in the United States. Some hospitals treated many more bites than they reported to ACHD. Animal bites remain a common injury and public health concern; ACHD should continue investigating bites and stress mandatory reporting of bites from health care providers to decrease underreporting
Optimization of Duplicate Pathogen Sequencing for Outbreak Detection
No full textBackground: Healthcare-associated infections (HAIs) are a well-known problem in medical care systems. Outbreak detection is necessary to identify and prevent potential HAI outbreaks. One new advancement in outbreak detection includes the use of proactive pathogen whole genome sequencing to detect outbreaks.
Methods and Results: Using data from the Enhanced Detection System for Healthcare-associated Transmission (EDS-HAT), this study aimed to determine the ideal time to perform repeat sequencing for select bacterial pathogens and to determine if there is a relationship between the tissue source the isolate is collected from and the days until a new infection. After narrowing the scope of the study to focus on P. aeruginosa (n=170), the study found that although not statistically significant, there does appear to be a difference in time to identify a new infection. Between those that did not have an isolate source change and those that did with those that did have an isolate source change from the original isolate identifying new infections at a more rapid rate. Based on restricted mean survival time estimates and Kaplan-Meier plots, we suggest that from day 1-36 there may be no need to resequence isolates, but after day 90 there is evidence indicating it would be beneficial to resequence patient isolates.
Conclusion: Although this study was unable to identify the ideal time to resequence patient isolates, we were able to characterize the typical time to infection which lays the groundwork for future research. Continuing this research will advance public health by enabling more rapid identification and containment of outbreaks, thereby mitigating their impact more effectively
For Black Women Who Have Reconsidered Flipping School Boards When Letters and Lawsuits Weren’t Enough: A Case Study on the Power Shifting Efforts of Black Women for a Better Education (BW4BE)
No full textFor decades, Pittsburgh Public Schools (PPS) has blatantly disregarded and ostracized Black caregivers and community members who have attempted to address concerns about the educational experience of Black students. The only moderately successful strategy was political activism led by Dr. Barbara Sizemore in the 1970s to secure a board majority, who fired an ineffective superintendent and hired a transformational leader who improved outcomes for Black children.
In 2020, Black Women for a Better Education (BW4BE) was formed to bring renewed visibility to the plight of Black PPS students. After an unsuccessful attempt to persuade the PPS board not to renew the contract of the previous superintendent, BW4BE formed a political action committee (PAC) to support candidates for PPS board. After successful cycles in 2021 and 2023, BW4BE secured a school board majority who is poised to transform outcomes for Black PPS students.
Through an artifact analysis, interviews with school board slate members, and a sister circle with BW4BE founders, this case study answered two inquiry questions, 1) What were the contributing factors to BW4BE’s success in shifting power from PPS by flipping the school board? 2) How does the Black mothering tradition influence the way Black women show up as community organizers for school reform?
Utilizing an endarkened feminist epistemology focused on Black women’s ways of knowing, the case study chronicled BW4BE’s inception, power shifting, and programming. Key findings about the success of BW4BE’s power shifting efforts included the community’s ongoing frustration with PPS, the desire for new school board representation, and circumstances surrounding the pandemic and racial reckoning of 2020. BW4BE’s foundation in the Black mothering tradition provided mission alignment, safety, and a hyperfocus on Black children.
This case study highlighted the need to revisit the history of Black educational activism in Pittsburgh, take bold action in the face of fear and hierarchy, and acknowledge the ancestral connections to Black education justice work. The study concluded with reflection on the possibilities for a school board majority, alternatives to traditional urban schooling for Black children, recommendations for education-focused role groups, and an overview of BW4BE’s future work
Black Girls Are Scientists: Science Identity Development and the Role of Culturally Sustaining Pedagogy in an Urban Science Classroom
No full textThe racial, gender, and class disparities of science self-efficacy among middle school
students create an equity barrier in middle school science students. Despite the research supporting
the need for inclusion, the STEM education community has a long history of eliminating culturally
diverse topics and people from the science curriculum. There are various long-standing challenges
and future opportunities and recommendations for better serving the 6-8 science/STEM education
needs of urban schools and communities. Teachers must prioritize students’ learning by actively
identifying scientists and inventors of various racial and ethnic backgrounds, incorporating diverse
scientists into their everyday curriculum, and learning the importance of students seeing
themselves in the science curriculum to increase students’ science self-efficacy and the likelihood
of pursuing a STEM-related career.
Through a pre-post survey and empathy and semi-structured interviews, this project
examined identity development using classroom observations, note taking, looking at student
work, and interviews to gain a deeper understanding of the science identity development of African
American girls within an urban school setting in the Midwest